Cargando…
β-Boswellic Acid Suppresses Breast Precancerous Lesions via GLUT1 Targeting-Mediated Glycolysis Inhibition and AMPK Pathway Activation
Breast carcinoma is a multistep progressive disease. Precancerous prevention seems to be crucial. β-Boswellic acid (β-BA), the main component of the folk medicine Boswellia serrata (B. serrata), has been reported to be effective in various diseases including tumors. In this work, we demonstrated tha...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194511/ https://www.ncbi.nlm.nih.gov/pubmed/35712503 http://dx.doi.org/10.3389/fonc.2022.896904 |
_version_ | 1784726745006473216 |
---|---|
author | Bie, Fengjie Zhang, Guijuan Yan, Xianxin Ma, Xinyi Zhan, Sha Qiu, Yebei Cao, Jingyu Ma, Yi Ma, Min |
author_facet | Bie, Fengjie Zhang, Guijuan Yan, Xianxin Ma, Xinyi Zhan, Sha Qiu, Yebei Cao, Jingyu Ma, Yi Ma, Min |
author_sort | Bie, Fengjie |
collection | PubMed |
description | Breast carcinoma is a multistep progressive disease. Precancerous prevention seems to be crucial. β-Boswellic acid (β-BA), the main component of the folk medicine Boswellia serrata (B. serrata), has been reported to be effective in various diseases including tumors. In this work, we demonstrated that β-BA could inhibit breast precancerous lesions in rat disease models. Consistently, β-BA could suppress proliferation and induce apoptosis on MCF-10AT without significantly influencing MCF-10A. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that β-BA may interfere with the metabolic pathway. Metabolism-related assays showed that β-BA suppressed glycolysis and reduced ATP production, which then activated the AMPK pathway and inhibited the mTOR pathway to limit MCF-10AT proliferation. Further molecular docking analysis suggested that GLUT1 might be the target of β-BA. Forced expression of GLUT1 could rescue the glycolysis suppression and survival limitation induced by β-BA on MCF-10AT. Taken together, β-BA could relieve precancerous lesions in vivo and in vitro through GLUT1 targeting-induced glycolysis suppression and AMPK/mTOR pathway alterations. Here, we offered a molecular basis for β-BA to be developed as a promising drug candidate for the prevention of breast precancerous lesions. |
format | Online Article Text |
id | pubmed-9194511 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-91945112022-06-15 β-Boswellic Acid Suppresses Breast Precancerous Lesions via GLUT1 Targeting-Mediated Glycolysis Inhibition and AMPK Pathway Activation Bie, Fengjie Zhang, Guijuan Yan, Xianxin Ma, Xinyi Zhan, Sha Qiu, Yebei Cao, Jingyu Ma, Yi Ma, Min Front Oncol Oncology Breast carcinoma is a multistep progressive disease. Precancerous prevention seems to be crucial. β-Boswellic acid (β-BA), the main component of the folk medicine Boswellia serrata (B. serrata), has been reported to be effective in various diseases including tumors. In this work, we demonstrated that β-BA could inhibit breast precancerous lesions in rat disease models. Consistently, β-BA could suppress proliferation and induce apoptosis on MCF-10AT without significantly influencing MCF-10A. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis suggested that β-BA may interfere with the metabolic pathway. Metabolism-related assays showed that β-BA suppressed glycolysis and reduced ATP production, which then activated the AMPK pathway and inhibited the mTOR pathway to limit MCF-10AT proliferation. Further molecular docking analysis suggested that GLUT1 might be the target of β-BA. Forced expression of GLUT1 could rescue the glycolysis suppression and survival limitation induced by β-BA on MCF-10AT. Taken together, β-BA could relieve precancerous lesions in vivo and in vitro through GLUT1 targeting-induced glycolysis suppression and AMPK/mTOR pathway alterations. Here, we offered a molecular basis for β-BA to be developed as a promising drug candidate for the prevention of breast precancerous lesions. Frontiers Media S.A. 2022-05-31 /pmc/articles/PMC9194511/ /pubmed/35712503 http://dx.doi.org/10.3389/fonc.2022.896904 Text en Copyright © 2022 Bie, Zhang, Yan, Ma, Zhan, Qiu, Cao, Ma and Ma https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Bie, Fengjie Zhang, Guijuan Yan, Xianxin Ma, Xinyi Zhan, Sha Qiu, Yebei Cao, Jingyu Ma, Yi Ma, Min β-Boswellic Acid Suppresses Breast Precancerous Lesions via GLUT1 Targeting-Mediated Glycolysis Inhibition and AMPK Pathway Activation |
title | β-Boswellic Acid Suppresses Breast Precancerous Lesions via GLUT1 Targeting-Mediated Glycolysis Inhibition and AMPK Pathway Activation |
title_full | β-Boswellic Acid Suppresses Breast Precancerous Lesions via GLUT1 Targeting-Mediated Glycolysis Inhibition and AMPK Pathway Activation |
title_fullStr | β-Boswellic Acid Suppresses Breast Precancerous Lesions via GLUT1 Targeting-Mediated Glycolysis Inhibition and AMPK Pathway Activation |
title_full_unstemmed | β-Boswellic Acid Suppresses Breast Precancerous Lesions via GLUT1 Targeting-Mediated Glycolysis Inhibition and AMPK Pathway Activation |
title_short | β-Boswellic Acid Suppresses Breast Precancerous Lesions via GLUT1 Targeting-Mediated Glycolysis Inhibition and AMPK Pathway Activation |
title_sort | β-boswellic acid suppresses breast precancerous lesions via glut1 targeting-mediated glycolysis inhibition and ampk pathway activation |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9194511/ https://www.ncbi.nlm.nih.gov/pubmed/35712503 http://dx.doi.org/10.3389/fonc.2022.896904 |
work_keys_str_mv | AT biefengjie bboswellicacidsuppressesbreastprecancerouslesionsviaglut1targetingmediatedglycolysisinhibitionandampkpathwayactivation AT zhangguijuan bboswellicacidsuppressesbreastprecancerouslesionsviaglut1targetingmediatedglycolysisinhibitionandampkpathwayactivation AT yanxianxin bboswellicacidsuppressesbreastprecancerouslesionsviaglut1targetingmediatedglycolysisinhibitionandampkpathwayactivation AT maxinyi bboswellicacidsuppressesbreastprecancerouslesionsviaglut1targetingmediatedglycolysisinhibitionandampkpathwayactivation AT zhansha bboswellicacidsuppressesbreastprecancerouslesionsviaglut1targetingmediatedglycolysisinhibitionandampkpathwayactivation AT qiuyebei bboswellicacidsuppressesbreastprecancerouslesionsviaglut1targetingmediatedglycolysisinhibitionandampkpathwayactivation AT caojingyu bboswellicacidsuppressesbreastprecancerouslesionsviaglut1targetingmediatedglycolysisinhibitionandampkpathwayactivation AT mayi bboswellicacidsuppressesbreastprecancerouslesionsviaglut1targetingmediatedglycolysisinhibitionandampkpathwayactivation AT mamin bboswellicacidsuppressesbreastprecancerouslesionsviaglut1targetingmediatedglycolysisinhibitionandampkpathwayactivation |